Using Genetic Tools to Dissect Neural Circuits for Social Communication

使用遗传工具剖析社交沟通的神经回路

• 批准号: 10152701
• 负责人: Richard D Mooney
• 金额: $ 51.39万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-11 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152701
• 关键词: Acoustics; Adult; Affect; Brain; Calcium; Chemicals; Communication; Data; Disease; Electrophysiology (science); Female; Foundations; Future; Genetic; Human; Image; Impairment; Individual; Influentials; Link; Mammals; Maps; Measures; Medial; Mediating; Mental disorders; Methods; Midbrain structure; Monitor; Mus; Neurodevelopmental Disorder; Neurons; Pattern; Perception; Play; Prefrontal Cortex; Production; Research; Role; Schizophrenia; Signal Transduction; Social Environment; Social Functioning; Social Interaction; Social Work; Testing; Ultrasonics; autism spectrum disorder; behavior measurement; cortex mapping; genetic approach; imaging modality; in vivo calcium imaging; in vivo imaging; innovation; insight; male; midbrain central gray substance; mind control; mouse model; neural circuit; neuropsychiatric disorder; novel; optogenetics; relating to nervous system; response; skills; social; social attachment; social communication; social deficits; sound; stem; tool; virus genetics; vocalization

Project Summary An inability to form and maintain social bonds typifies a wide range of neuropsychiatric and neurodevelopmental disorders. These social deficits stem in large part from impaired expressive and receptive vocal communication skills. Surprisingly, exactly how vocal communication promotes social affiliation is not well understood, in part because the underlying neural circuits remain poorly described. Here we propose the use of a novel genetic approach to selectively tag neurons that are active during social encounters that elicit vocalizations. We will combine this innovative method with in vivo imaging, electrophysiology, chemical and optogenetic perturbations of neural activity, and behavioral measurements to identify neural circuits that facilitate expressive and receptive aspects of vocal communication in the service of social affiliation. In Aim 1, we will test the idea that a specific subpopulation of neurons in the midbrain periaqueductal gray (PAG) is required for male and female mice to produce vocalizations used during their social interactions. In Aim 2, we will manipulate the activity of these PAG neurons to suppress or augment vocalization, allowing us to test the idea that these vocalizations promote social affiliation. In Aim 3, we will test the idea that prefrontal cortical (PFC) neurons that provide input to PAG vocalization neurons are important in regulating vocalization as a function of social context. In Aim 4, we will either reversibly silence or image PFC neurons that provide input to the PAG to test the idea that they play a role in generating affiliative social responses in males and females listening to a vocalizing individual. These studies will identify the neurons and circuits that gate vocalization during social encounters and promote social affiliation in response to these acoustic signals. This research will also build the foundation for future studies that explore how these circuits are affected in mouse models of neuropsychiatric disorders characterized by social communication and affiliation deficits, such as autism spectrum disorder and schizophrenia.

项目概要 无法形成和维持社会纽带是一系列神经精神和疾病的典型表现。 神经发育障碍。这些社交缺陷在很大程度上源于表达和接受能力受损 声音沟通技巧。令人惊讶的是，声音交流到底如何促进社会归属感并没有被研究。 很好理解，部分原因是底层神经回路的描述仍然很少。在这里我们建议 使用一种新颖的遗传方法来选择性地标记在社交遭遇中活跃的神经元，从而引发 发声。我们将把这种创新方法与体内成像、电生理学、化学和 神经活动的光遗传学扰动和行为测量来识别神经回路 促进声音交流的表达和接受方面，为社会归属服务。在目标 1 中， 我们将测试中脑导水管周围灰质 (PAG) 中特定神经元亚群的想法 雄性和雌性小鼠在社交互动中发出声音所必需的。在目标 2 中，我们 将操纵这些 PAG 神经元的活动来抑制或增强发声，使我们能够测试 认为这些发声可以促进社会归属感。在目标 3 中，我们将测试前额皮质 为 PAG 发声神经元提供输入的 (PFC) 神经元对于调节发声非常重要 社会背景的功能。在目标 4 中，我们将可逆地沉默或成像为 PFC 神经元提供输入 PAG 测试他们在男性和女性产生亲和社会反应方面发挥作用的想法 聆听一个发声的人。这些研究将确定控制发声的神经元和电路 在社交场合中，并根据这些声音信号促进社会归属感。这项研究将 也为未来的研究奠定了基础，探索这些电路如何在小鼠模型中受到影响 以社交沟通和归属缺陷为特征的神经精神疾病，例如自闭症 谱系障碍和精神分裂症。